Objective:

The primary objective of this Formative Children’s Center is to assemble a multidisciplinary team of experts to address critical gaps in our knowledge of the risks to children from Bisphenol A (BPA) and phthalate exposure. We will actively involve junior investigators and communicate the research findings to the health care community and public. Because both BPA and phthalates disrupt steroid hormone action, the studies will focus on endocrine-meditated outcomes including gonadal development and sexually dimorphic (differences between male and female) aspects of brain development and behavior.

Approach:

The impact of exposures during two developmental windows - the prenatal and the adolescent periods - will be assessed. At the heart of the research will be two human cohort studies - a pilot birth cohort in Urbana-Champaign, IL (Project 1;S.Schantz, PI) and a pilot adolescent cohort to be studied in the context of an ongoing study in New Bedford, MA (project 2; S. Korrick, PI). These studies will assess the relation of BPA or phthalate exposure to sexually dimorphic aspects of physical development and cognition in newborn infants and cognition in adolescent. This Center includes animal studies that will model the timing of exposure in the human cohorts. These studies will investigate mechanisms through which BPA disrupts male and female gonad development using transgenic (with genes from other organisms) and knockout (with specific genes deactivated) mouse models (Project 3; H. Yao, PI), and the impact of in utero or peripubertal BPA exposure on development of sexually dimorphic cortical brain regions and cognitive functions in a rat model (Project 4; J. Juraska, PI). While the two human studies will assess both phthalates and BPA, the animal studies will focus on BPA and later expand to include phthalates.

Expected Results:

Innovative use of analogous tests in animal and human studies, combined with mechanistic investigation (Projects 3,4), will optimize our ability to synthesize human and animal findings on BPA and phthalates. Data from these pilot studies is planned to provide the basis for further research studies. Central to the Center's long term goals are expansion of the pilot birth cohort into a larger prospective study with follow-up through puberty. This study would incorporate novel methods and approaches developed in the Formative Center. Another long term goal will be to expand the adolescent studies to include brain imaging. Studies in laboratory animal models would continue to play a key role, and would be used, both to explore mechanisms of action, and to identify key physical, biological and behavioral outcomes to assess in the children as they mature.

Supplemental Keywords:

Progress and Final Reports:

Subprojects under this Center:(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).R834593C001 Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral DevelopmentR834593C002 Adolescent Exposure to BPA/Phthalates Cognitive and Behavioral DevelopmentR834593C003 Mechanisms of In Utero BPA Exposure on Fetal Gonad DevelopmentR834593C004 Effects of Bisphenol A on the Developing Cortex

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.